Neurogenesis is a crucial process by which new neurons are formed in the brain through the conversion of Neuronal stem cells (NPCs). Altered neurogenesis has been identified in Alzheimer’s disease (AD), in both human brains and rodent models, yet the exact mechanism of the dysregulation is unknown. Over the past few years, growing evidence indicates that RNA-binding proteins (RBPs) play a critical role to fine-tune neurogenesis and mediate cortical development in the mammalian brain. Among these, the RNA-binding protein Staufen 2 (Stau2) plays an important role during neurogenesis unbalancing NSCs maintenance and differentiation, which is critical for brain development and functions. Importantly, STAU2 protein has been shown to be downregulated in AD, suggesting a possible role of STAU2 in impaired adult neurogenesis in AD
In this project, I will use induced pluripotent stem cells in combination with single-cell transcriptomic methods to characterize the unknown gene and protein networks regulated by STAU2 in neurogenesis at the single-cell level and investigate their relationship to altered neurogenesis in AD. This work will provide a solid molecular knowledge about the role of Stau2 in neural differentiation and its impact in neurogenesis in AD. Furthermore, I will develop a pipeline for the study of RBPs in human diseases and I will acquire indispensable scientific skills to become an independent research in Europe
Together, this study will provide a solid molecular knowledge of the role of RBPs in neural differentiation, enabling the development of new personalized medicine therapies, which is in compliance with the Horizon H2020 Health demographic change and wellbeing program.
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